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一种双特异性抗体方法,用于遗传性出血疾病的潜在预防性治疗

Prafull S Gandhi¹, Minka Zivkovic², Henrik Østergaard³

¹Hemab Therapeutics, Copenhagen, Denmark. prafull@hemab.com.

Nature cardiovascular research

|August 28, 2024

概括

一种新的双特异性抗体,HMB-001,显示出治疗遗传性出血障碍的前景,如Glanzmann血栓塞 (GT). 它有助于在受伤部位积累VIIa因子 (FVIIa),可能提供一种新的预防性治疗选择.

科学领域:

免疫学免疫学免疫学
血液学血液学血液学
药理学药理学是指药理学的学科.

背景情况:

遗传性出血障碍,如格兰兹曼血栓硬化 (GT),目前缺乏有效的预防性治疗.
在GT患者中,急性出血发作是通过输血或频繁的静脉注射复合活性凝固因子VII (rFVIIa) 进行管理的.

研究的目的:

描述HMB-001是一种新型双特异抗体,旨在预防性治疗遗传性出血障碍.
在临床前模型中评估HMB-001的疗效.

主要方法:

HMB-001旨在结合内源性FVIIa并将其向激活血小板上的TLT-1受体.
该抗体的药理动力学和血液静止潜力在非人类灵长类动物和小鼠中进行了评估.
格兰兹曼血栓塞的活体模型被用来评估HMB-001对血小板聚合的影响.

主要成果:

HMB-001成功地延长了半衰期,并增加了非人类灵长类动物内源性FVIIa的积累.
在小鼠出血研究中,通过TLT-1向显示了FVIIa血静活性通过抗体介导的增强.
在ex vivoGT模型中,HMB-001将FVIIa局部化到激活的血小板,并增强了纤维素依赖的血小板聚合.

结论:

HMB-001证明了作为Glanzmann血栓塞和其它遗传性出血障碍的皮下预防治疗的潜力.
双特异性抗体可能允许低频剂量治疗方案,以防止出血发作.

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